Clinical, Molecular, Functional, and Structural Characterization of CYP17A1 Mutations in Brazilian Patients with 17-Hydroxylase Deficiency

Horm Metab Res 2020; 52: 186-193 DOI: 10.1055/a-1100-706617-Hydroxylase-deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. The aim of the work was to study clinical, biochemical, and the follow up of 17OHD patients and evaluate the function and structure of CYP17A1 mutations. Brazilian patients (three 46, XX and four 46, XY; 17±1.9 years) with combined 17-hydroxylase/17,20-lyase deficiency were evaluated. CYP17A1 gene was sequenced. Functional analysis was performed transfecting COS7 cells, which were exposed to progesterone or 17α-hydroxypregnolone substrates. Hormones were determined by RIA or LC-MS/MS. Three-dimensional structural modeling was performed by Modeller software. All patients presented prepubertal female external genitalia, primary amenorrhea, hypergonadotrophic hypogonadism, hypokalemic hypertension, decreased cortisol, and increased ACTH and corticosterone levels. Five patients presented previously described mutations: p.W406R/p.W406R, IVS2–2A>C/p.P428L, and p.P428L/p.P428L. Two patients presented the compound heterozygous p.G478S/p.I223Nfs*10 mutations, whose CYP17A1 activity and the three dimensional structural modeling are originally studied in this paper. CYP17A1 activity of p.G478S was 13 and 58% against progesterone and 17-hydroxypregnenolone, respectively. The p.I223Nfs*10 caused a truncated in...
Source: Hormone and Metabolic Research - Category: Endocrinology Authors: Tags: Endocrine Care Source Type: research

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CONCLUSION: In hypertensive and diabetic patients, higher OPG values were associated with impaired LA function assessed by 2D-STE. In this high-risk patient group, serum OPG can be used as a risk predictor for LA mechanical dysfunction. PMID: 32462219 [PubMed - as supplied by publisher]
Source: Herz - Category: Cardiology Tags: Herz Source Type: research
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Source: Guardian Unlimited Science - Category: Science Authors: Tags: Coronavirus outbreak Infectious diseases Science Source Type: news
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Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
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Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
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Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
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Source: Hypertension in Pregnancy - Category: OBGYN Tags: Hypertens Pregnancy Source Type: research
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Source: Meta Gene - Category: Genetics & Stem Cells Source Type: research
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Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research
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Source: Diabetes Metab - Category: Endocrinology Authors: Tags: Endocrinol Diabetes Metab Case Rep Source Type: research
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